UMLS:C0043167 - FACTA Search

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Query: UMLS:C0043167 (pertussis)
19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of the present study was to investigate the proliferative effects of Ang II in human cardiac fibroblasts. The effects of Ang II in human cardiac fibroblasts on the 3H-thymidine incorporation, the cell number, the 3H-leucine incorporation and the total protein content were measured. The expression of receptor mRNA was performed by reverse transcription-polymerase chain reaction (RT-PCR). Ang II increased 3H-leucine incorporation in a concentration-dependent manner but not 3H-thymidine incorporation in primary cultures of human cardiac fibroblasts. The maximum effect (24 +/- 3% over control) was obtained at a concentration of 10 nM. There were no significant alterations of cell number or total protein content, suggesting that Ang II stimulated protein synthesis but did not induce hypertrophy. The accumulation of 3H-leucine was blocked by the AT1 receptor antagonist candesartan but not by the AT2 receptor antagonist PD123319. By using RT-PCR, both AT1 and AT2 receptors mRNA were found to be expressed in human cardiac fibroblasts. The selective MAPKK inhibitor PD098059, the protein kinase C inhibitor K252a or the phospholipase C inhibitor U73122 did not significantly inhibit Ang II augmented 3H-leucine incorporation. However, this was significantly blocked by the Ca2+-dependent protein kinase C inhibitor GO6976, the non-selective protein kinase inhibitor staurosporine and the tyrosine kinase inhibitor tyrphostin 25. The effects of Ang II were unaffected by the Gi-protein blocker pertussis toxin, indicating a Gi-protein-independent pathway. Ang II was synergistic with insulin but showed no significant increase on 3H-leucine incorporation when combined with PDGF or EGF. In summary, Ang II stimulates protein synthesis through AT1 receptors in human cardiac fibroblasts, but has no hypertrophic or hyperplastic effect. The response is mediated by a MAPKK-independent and Ca2+-sensitive PKC-dependent pathway.
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PMID:Angiotensin II type 1 receptors stimulate protein synthesis in human cardiac fibroblasts via a Ca2+-sensitive PKC-dependent tyrosine kinase pathway. 1071 68

Prostaglandin (PG) E(2) is an important modulator of the actions of angiotensin (Ang) II. In the present study, we investigated the renal microvascular actions of PGE(2) and the EP receptor subtypes involved. Ibuprofen potentiated Ang II-induced vasoconstriction in in vitro perfused normal rat kidneys and augmented afferent arteriolar, but not efferent arteriolar, responses in the hydronephrotic rat kidney model. This preglomerular effect of endogenous prostanoids was mimicked by exogenous PGE(2), which reversed Ang II-induced afferent arteriolar vasoconstriction at concentrations of 0.1 to 10 nmol/L without affecting the efferent arteriole. The PGE(2)-induced vasodilation was potentiated by the phosphodiesterase inhibitor Ro 20-1724 and was mimicked by 11-deoxy-PGE(1) (0.01 to 1 nmol/L). Butaprost, which acts preferentially at EP(2) receptors, was relatively ineffective. Whereas 0.1 to 10 nmol/L PGE(2) elicited vasodilation, higher concentrations (1 to 10 micromol/L) restored Ang II-induced afferent arteriolar vasoconstriction. This response was blocked by pertussis toxin (200 microg/mL) and was mimicked by the EP(1)/EP(3) agonist sulprostone (1 to 300 nmol/L). Reverse transcription-polymerase chain reaction of individually isolated afferent arterioles revealed the presence of message for EP(4) and all 3 EP(3) splice variants (alpha, beta, and gamma) but not EP(1) or EP(2). Our findings thus indicate that PGE(2) elicits both vasodilatory and vasoconstrictor actions on the afferent arteriole. The vasodilation is mediated by EP(4) receptors coupled to cAMP, presumably via G(alphas). The vasoconstriction is mediated by an EP(3) receptor coupled to G(alphai) and appears to reflect a functional antagonism of the EP(4)-induced vasodilation.
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PMID:Biphasic actions of prostaglandin E(2) on the renal afferent arteriole : role of EP(3) and EP(4) receptors. 1074 2

Angiotensin II activated mitogen-activated protein kinase (MAPK) (p42 and p44) in rat hepatocytes exposed to ethanol and the relevance of ethanol metabolism on this activation was investigated. Hepatocytes, isolated from rat liver, were treated with or without ethanol for 24 h. Angiotensin II, vasopressin, insulin, serum and epinephrine significantly increased hepatocyte MAPK activity. Platelet activating factor (PAF), tumor necrosis factor-alpha (TNF-alpha), and insulin-like growth factor-1 (IGF-1) had little effect on MAPK activation. Interestingly, among the above agonists, which activated hepatocyte MAPK, ethanol exposure potentiated only angiotensin II and epinephrine-stimulated MAPK. Thus, potentiation of MAPK by ethanol exhibited agonist selectivity. In contrast to several other cells, there was prevalence of p42 over p44 MAPK band in hepatocytes. Angiotensin II treatment caused a rapid activation (peak 5 min) of MAPK followed by a decrease to basal levels in 30 min. Exposure with 100 mM ethanol potentiated the angiotensin II stimulated MAPK activity. This potentiation was partially blocked by pertussis toxin suggesting it to be a G-protein-dependent event. Treatment of the hepatocytes with pyrazole (an inhibitor of ethanol metabolism) or acetaldehyde (an ethanol metabolite) had no effect on potentiation. Thus, ethanol potentiation of hepatocyte MAPK is agonist-selective and independent of ethanol metabolism.
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PMID:Ethanol alters angiotensin II stimulated mitogen activated protein kinase in hepatocytes: agonist selectivity and ethanol metabolic independence. 1086 21

Angiotensin II (AngII) receptors couple to a multitude of different types of G-proteins resulting in activation of numerous signaling pathways. In this study we examined the consequences of this promiscuous G-protein coupling on secretion. Chromaffin cells were voltage-clamped at -80 mV in perforated-patch configuration, and Ca(2+)-dependent exocytosis was evoked with brief voltage steps to +20 mV. Vesicle fusion was monitored by changes in membrane capacitance (DeltaC(m)), and released catecholamine was detected with single-cell amperometry. Ca(2+) signaling was studied by recording voltage-dependent Ca(2+) currents (I(Ca)) and by measuring intracellular Ca(2+) ([Ca(2+)](i)) with fura-2 AM. AngII inhibited I(Ca) (IC(50) = 0.3 nm) in a voltage-dependent, pertussis toxin (PTX)-sensitive manner consistent with G(i/o)-protein coupling to Ca(2+) channels. DeltaC(m) was modulated bi-directionally; subnanomolar AngII inhibited depolarization-evoked exocytosis, whereas higher concentrations, in spite of I(Ca) inhibition, potentiated DeltaC(m) fivefold (EC(50) = 3.4 nm). Potentiation of exocytosis by AngII involved activation of phospholipase C (PLC) and Ca(2+) mobilization from internal stores. PTX treatment did not affect AngII-dependent Ca(2+) mobilization or facilitation of exocytosis. However, protein kinase C (PKC) inhibitors decreased the facilitatory effects but not the inhibitory effects of AngII on stimulus-secretion coupling. The AngII type 1 receptor (AT1R) antagonist losartan blocked both inhibition and facilitation of secretion by AngII. The results of this study show that activation of multiple types of G-proteins and transduction pathways by a single neuromodulator acting through one receptor type can produce concentration-dependent, bi-directional regulation of exocytosis.
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PMID:Bidirectional modulation of exocytosis by angiotensin II involves multiple G-protein-regulated transduction pathways in chromaffin cells. 1086 35

Desensitization and phosphorylation of the endogenous angiotensin II AT(1) receptor were studied in clone 9 liver cells. Agonist activation of AT(1) receptors blunted the response to subsequent addition of angiotensin II. Partial inhibition of the angiotensin II-induced calcium response was observed when cells were pretreated with dibutyryl cyclic AMP, tetradecanoyl phorbol acetate (TPA), vasopressin, or lysophosphatidic acid. All of these desensitization processes were associated with receptor phosphorylation. Angiotensin II-induced AT(1) receptor phosphorylation was partially blocked by the protein kinase C inhibitor bisindolylmaleimide I and by phosphoinositide 3-kinase inhibitors (wortmannin and LY294002); the actions of these inhibitors were not additive. Pertussis toxin pretreatment of cells also partially inhibited angiotensin II-induced AT(1) receptor phosphorylation. TPA-induced AT(1) receptor phosphorylation was completely blocked by bisindolylmaleimide I. AT(1) receptor phosphorylation was also induced by vasopressin and lysophosphatidic acid, and these effects were partially inhibited by bisindolylmaleimide I. Angiotensin II increased Akt/PKB (protein kinase B) phosphorylation and protein kinase C membrane association. The effect on Akt/PKB phosphorylation was blocked by phosphoinositide 3-kinase inhibitors. These findings indicate that clone 9 cells exhibit both homologous and heterologous desensitization in association with AT(1) receptor phosphorylation. In these hepatic cells, angiotensin II-induced receptor phosphorylation involves pertussis toxin-sensitive and -insensitive G proteins, and is mediated in part through protein kinase C and phosphoinositide 3-kinase.
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PMID:Angiotensin AT(1) receptor phosphorylation and desensitization in a hepatic cell line. Roles of protein kinase c and phosphoinositide 3-kinase. 1117 53

In spontaneously hypertensive rats (SHR), hypertension is mediated in part by an enhanced renovascular response to angiotensin (Ang) II. Pertussis toxin normalizes renovascular responses to Ang II and lowers blood pressure in SHR, suggesting a role for altered G(i) signaling in the enhanced renovascular response to Ang II in SHR. To further investigate this hypothesis, we measured reductions in renal blood flow and increases in renovascular resistance in response to intrarenal infusions of Ang II in the presence and absence of coactivation of alpha(2)-adrenoceptors (ie, receptors selectively coupled to G(i)) with UK 14,304 in adrenalectomized, renal-denervated, captopril-pretreated SHR and normotensive Wistar-Kyoto rats. In SHR, but not Wistar-Kyoto rats, UK 14,304 markedly enhanced renovascular responses to Ang II and vasopressin. However, UK 14,304 did not enhance renovascular responses to methoxamine (alpha(1)-adrenoceptor agonist) in either strain. In uninephrectomized, normotensive Sprague-Dawley animals and in Sprague-Dawley rats with nongenetic hypertension induced by uninephrectomy, chronic administration of deoxycorticosterone acetate, and 1% saline as drinking water, UK 14,304 had little or no effect on renovascular responses to Ang II. In SHR, intrarenal infusions of U73122, a phospholipase C/D inhibitor, blocked the enhancement of renovascular responses to Ang II by UK 14,304. We conclude that activation of alpha(2)-adrenoceptors selectively enhances renovascular responses to Ang II and vasopressin in vivo in animals with genetic hypertensive but not in normotensive animals or animals with acquired hypertension. These results suggest that in SHR, there is a genetically mediated enhanced cross talk between the G(i) signal transduction pathway and signal transduction pathways activated by Ang II and vasopressin, but not methoxamine, and involving phospholipase C and/or D.
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PMID:Enhanced interaction between renovascular alpha(2)-adrenoceptors and angiotensin II receptors in genetic hypertension. 1156 4

Angiotensin (Ang) II has 2 major receptor isoforms, Ang type 1 (AT(1)) and Ang type (AT(2)). AT(1) transphosphorylates epidermal growth factor receptor (EGFR) to activate extracellular signal-regulated kinase (ERK). Although AT(2) was shown to inactivate ERK, the action of AT(2) on EGFR activation remains undefined. Using AT(2)-overexpressing vascular smooth muscle cells from AT(2) transgenic mice, we studied these undefined actions of AT(2). Maximal ERK activity induced by Ang II was increased 1.9- and 2.2-fold by AT(2) inhibition, which was abolished by orthovanadate but not okadaic acid or pertussis toxin. AT(2) inhibited AT(1)-mediated EGFR tyrosine phosphorylation by 63%. The activity of SHP-1 tyrosine phosphatase was significantly upregulated 1 minute after AT(2) stimulation and association of SHP-1 with EGFR was increased, whereas AT(2) failed to tyrosine phosphorylate SHP-1. Stable overexpression of SHP-1-dominant negative mutant completely abolished AT(2)-mediated inhibition of EGFR and ERK activation. AT(1)-mediated c-fos mRNA accumulation was attenuated by 48% by AT(2) stimulation. Induction of fibronectin gene containing an AP-1 responsive element in its 5'-flanking region was decreased by 37% after AT(2) stimulation, corresponding to the results of gel mobility assay with the AP-1 sequence of fibronectin as a probe. These findings suggested that AT(2) inhibits ERK activity by inducing SHP-1 activity, leading to decreases in AP-1 activity and AP-1-regulated gene expression, in which EGFR dephosphorylation plays an important role via association of SHP-1.
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PMID:Angiotensin II type 2 receptor inhibits epidermal growth factor receptor transactivation by increasing association of SHP-1 tyrosine phosphatase. 2370 57

Vascular smooth muscle cell (VSMC) proliferation is a key feature in the development of atherosclerosis and restenosis after angioplasty, which can occur in response to many different humoral and mechanical stimuli. We investigated the growth promoting activities of two potent vasoactive substances, angiotensin II (Ang II) and serotonin (5-HT), on cultured rabbit VSMCs. Growth-arrested VSMCs were incubated with serum-free medium containing different concentrations of Ang II in the presence or absence of 5-HT. [3H]thymidine incorporation into VSMC DNA was measured as an index of cell proliferation. Ang II and 5-HT stimulated DNA synthesis in a dose-dependent manner with a maximal effect at 1.75 microM for Ang II (202%) and 50 microM for 5-HT (205%). When added together, low concentrations of Ang II (1 microM) and 5-HT (5 microM) synergistically induced DNA synthesis (363%). Candesartan (1 microM), an AT(1) receptor antagonist, but not PD 123319 (1 microM), an AT(2) receptor antagonist, inhibited the mitogenic effect on Ang II and its interaction with 5-HT. Sarpogrelate (10 microM), a 5-HT(2A) receptor antagonist, and pertussis toxin (10 ng/ml) inhibited the mitogenic effect of 5-HT and its interaction with Ang II. The protein kinase C inhibitor Ro 31-8220 (0.1 microM), the Raf-1 inhibitor radicicol (10 microM), and the MAPK kinase inhibitor PD 098059 (10 microM) abolished mitogenic effects of Ang II and 5-HT, and also their synergistic interaction. The JAK2 inhibitor AG 490 (10 microM) had only a minimal inhibitory effect of Ang II-induced DNA synthesis but significantly inhibited the interaction of Ang II with 5-HT. The synergistic effect on Ang II (1 microM) with 5-HT (5 microM) on DNA synthesis was completely reversed by the combined use of both candesartan (1 microM) and sarpogrelate (10 microM). Our results suggest that Ang II and 5-HT exert a synergistic interaction on VSMC proliferation via AT(1) and 5-HT(2A) receptors. The activation of MAPK and JAK/STAT pathways may explain the synergistic interaction between Ang II and 5-HT.
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PMID:Serotonin potentiates angiotensin II--induced vascular smooth muscle cell proliferation. 1173 Aug 6

We investigated the role of angiotensin II type 1 (AT(1)) receptors in angiotensin II-induced actin reorganization and the signaling pathways of the response in pleural mesothelial cells. The effects of angiotensin II on actin reorganization in pleural mesothelial cells were evaluated by dual fluorescence labeling of filamentous (F) and monomeric (G) actin with fluorescein isothiocyanate (FITC)-labeled phalloidin and Texas Red-labeled DNase I, respectively. Angiotensin II (10 microM) induced actin reorganization in the presence and the absence of extracellular Ca(2+). An angiotensin AT(1) receptor antagonist ([Sar(1),Ile(8)]angiotensin II) inhibited angiotensin II-induced actin reorganization. Pretreatment with C3 exoenzyme or tyrosine kinase inhibitors significantly reduced angiotensin II-induced actin reorganization. However, pertussis toxin, phosphatidylinositol-3-kinase and protein kinase C inhibitors had no effect on these responses. These results suggest that angiotensin II-induced actin reorganization in pleural mesothelial cells is extremely dependent on the angiotensin AT(1) receptor coupled with pertussis toxin-insensitive heterotrimeric G proteins, Rho GTPases and tyrosine phosphorylation pathways.
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PMID:Involvement of Rho and tyrosine kinase in angiotensin II-induced actin reorganization in mesothelial cells. 1183 42

Angiotensin II (AII) in 1-10 nM concentrations has an in vivo immunostimulating effect on human neutrophils. The release of superoxide anions and leukotrienes (LTs) is significantly increased by 10 nM AII-stimulated neutrophils of patients with hypercholesterolaemia (HCH). These oxidizing agents may be involved in the damage of vessel walls, i.e., in atherosclerotic plaque formation. To clarify the receptor types and signal pathways in neutrophils of healthy controls and patients, inositol trisphosphate (IP(3)) production and Ca(2+) signalling were studied. Neutrophils were pretreated before AII stimulation with different inhibitory drugs. In control cells, the stimulation occurred predominantly through pertussis toxin-sensitive, type angiotensin 1 receptors. This induced IP(3) production and Ca(2+) signalling from intracellular pools. In neutrophils of hypercholesterolaemic patients, the enhanced release of oxidizing agents was dependent more on type angiotensin 2 than type angiotensin 1 receptors. After stimulation, there was no IP(3) production detected. The Ca(2+) signalling was lower than in control cells and was dependent on extracellular Ca(2+).
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PMID:Altered signal pathway in angiotensin II-stimulated neutrophils of patients with hypercholesterolaemia. 1203 60

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